DESCRIPTION (provided by investigator): The objective of this study is to examine changes in personality traits in the preclinical phase of Alzheimer's disease (AD) and to identify early markers of the disease before the onset of dementia. Personality traits refer to the emotional, cognitive, and behavioral characteristics of a person. Changes in personality are one of the clinical criteria for the diagnosis of dementia, and changes in the five major dimensions of personality (increases in neuroticism and declines in extraversion, openness, agreeableness, and conscientiousness) have been consistently observed with the onset and progression of dementia. It is unknown, however, whether changes in the major dimensions of personality begin before the onset of dementia. For example, changes in the personality domain of conscientiousness, such as impaired motivation and loss of interest, and changes in neuroticism, such as increased emotional vulnerability and irritability, could precede the manifestation of cognitive impairments. There is thus the need for prospective, longitudinal studies to systematically examine personality change before the onset of dementia. This proposed study will examine data from the Baltimore Longitudinal Study of Aging (BLSA), an ongoing community-based cohort study. Since 1980, 1,725 participants have completed a self-reported measure of personality on multiple occasions, on average 5 assessments per person. In addition, a subset of participants had their personality rated by their spouse. BLSA participants were genotyped and their clinical and cognitive status has been evaluated at regularly scheduled visits. The BLSA includes extensive neuroimaging and an autopsy sub-study of subjects who agreed to postmortem brain examinations. This proposed study will test the hypothesis that changes in personality can be detected in the preclinical phase of AD. By examining data that span more than a decade (up to 31 years) before the onset of dementia, this study will determine at what stage and which specific personality traits change in the preclinical phase of AD. Further, the study will determine whether there are changes in personality specific to AD as compared to other dementias and whether sex and APOE ?4 carrier status moderate the change in personality. In an effort to understand the neurobiological basis of personality changes, the study will also test whether personality changes are associated with the extent of AD neuropathology (amyloid plaques and neurofibrillary tangles). Thus, the proposed study provides the unprecedented opportunity to systematically evaluate the progression of personality change in the crucial preclinical phase of AD. Such changes may represent an early marker of the disease and can aid in the timely diagnosis of AD. Early detection allows the person with the condition and their family to have conversations about their wishes and make plans for future care before the worsening of decisional capacity. Early detection can also expedite the implementation of eventual prevention and treatment interventions prior to the onset of clinical dementia.